St. Jude Reference #SJ-12-0036
Researchers at St. Jude discovered an activatable fusion protein, composed of the Receptor Interacting Protein Kinase 3 (RIPK3) linked to 2 FKBP fragments (FV domains), that induces necroptosis. The FV domains specifically bind a modified version of the drug rapamycin, which causes the RIPK3 to dimerize or oligomerize; with oligomerization of RIPK3 triggering cell death.
This construct may be useful for treating certain types of cancer and autoimmunity. It can also eliminate upstream activators of RIPK3, allowing direct assessment of downstream effectors using techniques such as siRNA screening, chemical screening, and phosphoproteomics.
Cell Therapy, RIPK3, cancer, immunomodulation
Granted Patents or Published Applications
US patent application - publication #2016-0160189
Related Scientific References
Tait SW, Oberst A, Quarato G, Milasta S, Haller M, Wang R, Karvela M, Ichim G, Yatim N, Albert ML, Kidd G, Wakefield R, Frase S, Krautwald S, Linkermann A, Green DR. Widespread mitochondrial depletion via mitophagy does not compromise necroptosis. Cell Rep. 2013 Nov 27;5(4):878-85. doi: 10.1016/j.celrep.2013.10.034. Epub 2013 Nov 21.
See also: YS Cho et al Cell 2009, S He et al Cell 2009; A. Oberst et al Nature 2011.
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